title: Whole-body imaging of high-dose ionizing irradiation-induced tissue injuries using 99mTc-duramycin.
abstract: High-dose ionizing irradiation can cause extensive injuries in susceptible tissues. A noninvasive imaging technique that detects a surrogate marker of apoptosis may help characterize the dynamics of radiation-induced tissue damage. The goal of this study was to prove the concept of imaging the temporal and spatial distribution of damage in susceptible tissues after high-dose radiation exposure, using (99m)Tc-duramycin as a phosphatidylethanolamine-binding radiopharmaceutical.
  
  
  METHODS
  Rats were subjected to 15 Gy of total-body irradiation with x-rays. Planar whole-body (99m)Tc-duramycin scanning (n = 4 per time point) was conducted at 24, 48, and 72 h using a clinical γ-camera. On the basis of findings from planar imaging, preclinical SPECT data were acquired on control rats and on irradiated rats at 6 and 24 h after irradiation (n = 4 per time point). Imaging data were validated by γ-counting and histology, using harvested tissues in parallel groups of animals (n = 4).
  
  
  RESULTS
  Prominent focal uptake was detected in the thymus as early as 6 h after irradiation, followed by a gradual decline in (99m)Tc-duramycin binding accompanied by extensive thymic atrophy. Early (6-24 h) radioactivity uptake in the gastrointestinal region was detected. Significant signal was seen in major bones in a slightly delayed fashion, at 24 h, which persisted for at least 2 d. This finding was paralleled by an elevation in signal intensity in the kidneys, spleen, and liver. The imaging results were consistent with ex vivo γ-counting results and histology. Relatively high levels of apoptosis were detected from histology in the thymus, guts, and bones, with the thymus undergoing substantial atrophy.
  
  
  CONCLUSIONS
  As a proof of principle, this study demonstrated a noninvasive imaging technique that allows characterization of the temporal and spatial dynamics of injuries in susceptible tissues during the acute phase after high-dose ionizing irradiation. Such an imaging capability will potentially be useful for global, whole-body, assessment of tissue damage after radiation exposure. These data, in turn, will contribute to our general knowledge of tissue susceptibility to ionizing irradiation, as well as the onset and progression of tissue injuries.
authors.affiliation: Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Johnson
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001430:Bacteriocins; D005240:Feasibility Studies; D005260:Female; D021621:Imaging, Three-Dimensional; D064847:Multimodal Imaging; D015609:Organotechnetium Compounds; D049268:Positron-Emission Tomography; D011829:Radiation Dosage; D011833:Radiation Injuries, Experimental / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology*; D051381:Rats; D014057:Tomography, X-Ray Computed; D051598:Whole Body Imaging
chemical_list: D001430:Bacteriocins; D015609:Organotechnetium Compounds; C578182:technetium 99m HYNIC-duramycin
keywords: 99mTc-Duramycin; apoptosis; phosphatidylethanolamine; radiation injuries